Quantitative phase microscopy of biological cell dynamics by wide-field digital interferometry

Interferometric phase measurements of wide-field images of biological cells provide a quantitative tool for cell biology, as well as for medical diagnosis and monitoring. Visualizing rapid dynamic cell phenomena by interferometric phase microscopy can be performed at very fast rates of up to several thousands of full frames per second, while retaining high resolution and contrast to enable measurements of fine cellular features. With this approach, no special sample preparation, staining, or fluorescent labeling is required, and the resulting phase profiles yield the optical path delay profile of the cell with sub-nanometer accuracy. In spite of these unique advantages, interferometric phase microscopy has not been widely applied for recording the dynamic behavior of live cells compared to other traditional phase microscopy methods such as phase contrast and differential interference contrast (DIC) microscopy, which are label free but inherently qualitative. Recent developments in the field of interferometric phase microscopy are likely to result in a change in this situation in the near future. Through careful consideration of the capabilities and limitations of interferometric phase microscopy, important new contributions in the fields of cell biology and biomedicine will be realized. This chapter presents the current state of the art of interferometric phase microscopy of biological cell dynamics, the open questions in this area, and specific solutions developed in our laboratory.